The field of the invention relates to substituted pyrrolo[2,3-d]pyrimidines. In particular, the field of the invention relates to substituted pyrrolo[2,3-d]pyrimidines for the treatment of cell proliferation diseases and disorders such as cancer.
While treatment options have improved in recent years, cancer remains the second leading cause of death in the United States. Many cancers lack effective treatments and have poor long-term prognoses. In particular, multiple myeloma is the second most prevalent hematological malignancy and kills over 10,000 people annually. The median survival from this type of cancer is approximately 5-7 years. Even with the advent of several new chemotherapies, only 25-35% of patients respond to these drugs. Additional treatment options are necessary for patients who fail to respond to current therapies and for those who develop resistance to current therapies.
Here, as part of an effort to discover and evaluate new small molecules that have the potential for treating human cancer, in particular hematological malignancies, we have identified a series of novel substituted pyrrolo[2,3-d]pyrimidine compounds that display potent in vitro cytotoxicity against cancer cells. These compounds present unique substitution patterns that impart on them activity against a variety of human cancer cell lines. Compound analogs have been synthesized and tested to generate robust structure-activity relationships based on multiple sites of diversification. Lead compounds possess excellent profiles as potential therapeutics based on a variety of physiochemical properties. These new compounds therefore hold promise as new potential treatments for cancer and other proliferative diseases.